This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Optical clearing of human skin;preliminary results of in vitro and in vivo studies Background: Skin is a highly scattering structure due to its complex morphology. Light-based diagnostic and therapeutic procedures lose a significant amount of light due to scattering. Lack of adequate penetration for diagnostic and therapeutic procedures is often compensated by increasing the power and radiant exposure of the incident light. Such measures often lead to un-desirable side effects such as epidermal and dermal injury leading to infection, blistering and even scarring. Reduction in skin scattering is therefore desirable for better light penetration thru intact human skin. Material and methods: chemical combinations of different concentrations of polypropylene glycol and polyethylene glycol were created. Optical clearing potential of a variety of chemicals was tested in vitro, using full thickness human skin. The optical clearing potential of various chemicals was also tested in vivo, by using optical coherence tomography and measuring the maximum depth imaged non-invasively. Light-based therapeutic procedures such as laser assisted hair removal, tattoo removal and laser treatment of port-wine stains was also tested in vivo, using the topically applied optical clearing agents, as part of an IRB approved study on-going at Beckman laser clinic. Results: chemical combinations of PPG and PEG in a specific ratio produced significant clearing of the skin in vitro as well in vivo. The maximum depth of skin as imaged with OCT was markedly increased. Light-based therapeutic procedures produced significantly less epidermal and dermal side effects when combined with the topically applied clearing agent. Additionally, better light penetration for therapeutic procedures also reduced the number of treatments required to achieve the desired result. Conclusions: topically applied optical clearing agents reduce surface, as well as dermal scattering of light, as it penetrates intact human skin in vitro and in vivo. light-based diagnostic as well as therapeutic procedures can benefit significantly if optical clearing of the skin is performed prior to the desired procedure. Additionally, reduction in scattering provides epidermal as well as dermal protection, thereby reducing the incidence of significant side effects such as infection, pigmentary changes, blistering and scarring.